First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

Synthesis of trans-Fused 3,6-Anhydro Hexofuranose Frameworks via Catalytic Hydrogenolysis Triggered Debenzylative Intramolecular Acetalation.

Presented herein is the chemical construction of unprecedented 3,4-trans-3,6-anhydro hexofuranose frameworks. The disfavored 3,6-anhydro hexofuranosides were effectively established by Pd-catalyzed debenzylative intramolecular acetalation for the first time. The critical roles of benzyl protection and Pd as catalyst were demonstrated.

Frailty impacts all-cause mortality after endovascular abdominal aortic aneurysm repair: a retrospective cohort study.

Objective: This study aimed to evaluate the impact of frailty and inflammation on all-cause mortality in patients with abdominal aortic aneurysm (AAA) who underwent endovascular aneurysm repair (EVAR), and key risk factors were also explored.

Methods: A retrospective analysis was conducted on 174 patients with AAA who underwent EVAR at Beijing Hospital between 2016 and 2024. Frailty was assessed using the modified five-item Frailty Index (mFI-5).

The investigation of the interaction of warangalone with transferrin as a therapeutic biological macromolecule and the formation of a protein-ligand nanocomplex with superior anticancer activity against lung cancer cells.

Though warangalone has shown anticancer properties against breast cancer cells, its colloidal stability and therapeutic index ought to be improved using a potential strategy, especially via protein-based (nano)carriers. In this research, transferrin was used as a plasma protein for the development of the warangalone-transferrin NPs. To investigate the mechanism underlying the formation of this complex, the interaction between warangalone and transferrin, as well as transferrin NPs, was analyzed using spectroscopic methods.

[Qualitative and quantitative analysis of chemical components of Dracocephalum moldavica based on UPLC-Q-TOF-MS/MS and UPLC].

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to rapidly identify the chemical components in Dracocephalum moldavica, and UPLC was employed to determine the content of its main components. MS analysis was performed using an electrospray ionization(ESI) source and data were collected in the negative ion mode. By comparing the retention time and mass spectra of reference compounds, and using a self-built compound database and the PubChem database, 68 compounds were identified from D.

Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation.

Rationale: Coronary artery plaques often develop in regions subjected to disturbed shear stress (DSS), yet the mechanisms underlying this phenomenon remain poorly understood. Our study aimed to elucidate the unknown role of MAPK6 in shear stress and plaque formation.

Methods: In vitro and in vivo experiments, RNA-seq, CO-IP and proteomic analysis, combined with single-cell RNA-seq datasets were used to reveal the upstream and downstream mechanisms involved.

Targeting the ALKBH5-NLRP3 positive feedback loop alleviates cardiomyocyte pyroptosis after myocardial infarction.

Several studies have associated the epitranscriptomic RNA modification of N6-methyladenosine (mA) with cardiovascular diseases; however, how mA modification affects cardiomyocyte pyroptosis after myocardial infarction (MI) remains unknown. Here, we showed that AlkB homolog 5 (ALKBH5), an mA demethylase, is crucial in cardiomyocyte pyroptosis after MI. We used MI rat and mouse models, a cell hypoxia model of rat primary cardiomyocytes (RCMs), and rat embryonic ventricle cell line (H9c2) to explore the functional role of mA modification and ALKBH5 in the heart and cardiomyocytes.

Msx1-Modified Rat Bone Marrow Mesenchymal Stem Cell Therapy for Rotator Cuff Repair: A Comprehensive Analysis of Tendon-Bone Healing and Cellular Mechanisms.

This study investigates the therapeutic potential of Msx1-overexpressing bone marrow mesenchymal stem cells (BMSCs) in enhancing tendon-bone healing in rotator cuff injuries. BMSCs were genetically modified to overexpress Msx1 and were evaluated in vitro for their proliferation, migration, and differentiation potential. Results demonstrated that Msx1 overexpression significantly increased BMSC proliferation and migration while inhibiting osteogenic and chondrogenic differentiation.

Causal relationship between Hashimoto's thyroiditis and non-ischemic cardiomyopathy and the mediating role of inflammatory cytokines: Evidence from genetic association analysis.

Background: Previous studies report that Hashimoto's thyroiditis (HT) may be associated with non-ischemic cardiomyopathy (NICM); However, the causal relationship remains to be elucidated. Here, we aimed to investigate the causal relationship between HT and NICM through Mendelian randomization (MR) and explore the potential mediating role of inflammatory cytokines within this association.

Methods: The bidirectional two-sample MR, multivariable MR and mediation MR analyses were conducted based on genome-wide association study summary datasets, and MR results were further supported by multiple sensitivity analysis methods.

Regulatory factor X-5/SCL/TAL1 interruption site axis promotes aerobic glycolysis and hepatocellular carcinoma cell stemness.

The incidence and development of various tumors, such as hepatocellular carcinoma (HCC), are linked to tumor stem cells. Although research has revealed how important SCL/TAL1 interruption site (STIL) is in many human tumors, the impact of STIL on HCC stem cells is poorly understood. This study aimed to examine the regulatory mechanisms and the function of STIL in the stemness of HCC tumor cells.

ALKBH5 promotes cardiac fibroblasts pyroptosis after myocardial infarction through Notch1/NLRP3 pathway.

Through bioinformatics screening, we previously found that AlkB homolog 5 (ALKBH5) expression, an mA demethylase, was higher in patients with heart failure than in the normal population. This study aimed to investigate the molecular mechanisms by which ALKBH5 regulates heart failure. We established a myocardial infarction (MI)-induced heart failure model in rats in vivo and an in vitro hypoxia model using rat primary cardiac fibroblasts (RCFs).

[One new galloyl derivative from Isodon henryi].

Seven compounds(1-7) were isolated from Isodon henryi through silica gel, Sephadex LH-20, ODS, MCI column chromatography and semi-preparative HPLC. Their structures were identified as isogallicacid(1), caffeic acid(2), syringic acid(3), protocatechuic acid(4), oresbiusin A(5), lophanthoside A(6), and 8-hydroxypinoresinol(7), by spectroscopic techniques including HR-MS, IR, UV, NMR, and ECD. Compound 1 was a new galloyl derivative.

[Differences in components and anti-inflammatory and analgesic activities of two phase states of Wuzhuyu Decoction].

This study rapidly identified and quantified the chemical components of the Wuzhuyu Decoction nanophase(WZYD-N) and suspension phase(WZYD-S) using ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS). Based on preliminary pharmacodynamic experiments and network pharmacology analysis, the differential anti-inflammatory and analgesic activities of WZYD-N and WZYD-S were explored to understand their pharmacodynamic basis. WZYD-N and WZYD-S were separated by differential centrifugation-dialysis, and their particle size, Zeta potential, PDI, and morphology were characterized by dynamic light scattering and transmission electron microscopy.

[Quality analysis of Xueshuan Xinmaining Tablets and Capsules based on UPLC-Q/TOF-MS and UPLC-QQQ-MS/MS].

Xueshuan Xinmaining Tablets and Capsules are two Chinese patent medicines with the same prescription, different preparation methods but the same function of replenishing Qi, activating blood, opening orifices, and relieving pain. Xueshuan Xinmaining Capsules were qualitatively analyzed by UPLC-Q/TOF-MS for the first time, and 61 compounds were identified, including 9 phenolic acids, 10 bufadienolides, 15 saponins, 5 bile acids, and 22 other compounds. The chemical composition was slightly different between Xueshuan Xinmaining Tablets and Capsules.

[Identification and analysis of CmOMT gene family in Chrysanthemum morifolium].

Chrysanthemum morifolium is rich in hydroxyflavonoids and methoxyflavonoids(OMFs), and dissecting the biosynthetic pathway of OMFs in Ch. morifolium is of great theoretical and economic value because of the diverse physiological activities and pharmacological effects of OMFs. To investigate the biosynthetic pathway of OMFs in Ch.

[Suggestions for revision of quality standards of red yeast rice for medicinal and edible purposes in China].

Red yeast rice(RYR) is fermented rice with a long history of medicinal and edible purposes in China. RYR has gained global popularity, particularly in South and Southeast Asia, Europe, and America, due to its blood lipid-lowering effect and abundant edible natural pigments. However, concerns have been aroused regarding the safety of RYR due to increasing reports on the side effects and toxicity associated with statins and mycotoxins in RYR.

[UPLC-Q-TOF-MS/MS qualitative analysis and HPLC determination of triterpenoids in Ganoderma lucidum spores].

Ganoderma spores are the dry and mature spores of G. lucidum or G. sinense of Polyporaceae, with strong immunity-improving, anti-tumor, and anti-oxidant activities.

[Mechanisms of Shaoyao Gancao Decoction in treatment of rheumatoid arthritis based on UPLC-Orbitrap-MS~2, network pharmacology, and cellular experiment verification].

Shaoyao Gancao Decoction(SGD) is a classic formula used in the clinical treatment of joint diseases, such as rheumatoid arthritis(RA), though its mechanism of action remains unclear. This study aimed to explore the mechanism of SGD in treating RA through chemical and network pharmacology analyses, combined with cellular experiments. UPLC-Orbitrap-MS~2 was used to qualitatively analyze SGD and drug-containing serum of rats after oral administration of SGD, thereby identifying the chemical composition and plasma components of SGD.

[Enzymatic reaction pattern of saponins in Gynostemma pentaphyllum and identification of their transformed products].

The activity of rare saponins is generally better than that of their prototypes. There are significant differences in the proportions and pharmacological effects of rare saponins/prototype saponins in Gynostemma pentaphyllum samples dried with different methods, which may be related to the reaction catalyzed by glucosidase. To explore the pattern of the enzymatic reaction catalyzed by glucosidase during the processing of G.

Progress in the study of curcumin metabolism .

Curcumin has diverse biological functions, especially antioxidant and anti-inflammatory properties, but clinical trials have been hindered by its low bioavailability and pharmacokinetic properties. To achieve therapeutic efficacy, understanding curcumin's metabolism is crucial. We reviewed current research on curcumin metabolism in PubMed, Google Scholar, and CNKI.

Run-Mu-Ling Granules Mitigate Ocular Surface Inflammatory Injury Associated with Dry Eye by Suppressing the NLRP3/GSDMD-Mediated Pyroptosis Pathway.

Purpose: Run-Mu-Ling granules (RMLG), a traditional Chinese medicinal formula, are used to treat dry eye (DE); however, the underlying mechanism remains poorly understood. This study aimed to elucidate the potential molecular mechanisms by which RMLG alleviates ocular surface inflammation in DE.

Methods: We established an in-vivo DE rat model and in-vitro human corneal epithelial cell line (HCEC) injury models.

Sesquiterpene enantiomers from Alismatis Rhizoma.

A pair of dinor-sesquiterpene enantiomers (1a/1b), eight pairs of guaiane-type sesquiterpenes enantiomers (2a/2b, 3a/3b, 4a/4b, 5a/5b, 6a/6b, 7a/7b, 8a/8b, 9a/9b) and two guaiane-type sesquiterpenes (10, 11), including eleven undescribed ones (1a, 1b, 2a, 2b, 3a, 3b, 4a, 5b, 6a, 10, and 11), were isolated from the aqueous extract of Alismatis Rhizoma. The structures were elucidated by combining 1D and 2D NMR and HRESIMS spectroscopic data. The absolute configurations were determined by experimental and calculated ECD spectra, [Mo(OAc)]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of similar analogs.

Reinforcing Photogenerated Carrier Extraction of Environment-Friendly InP/ZnSeS Quantum Dots for High-Performing Photoelectrochemical Photodetection and Solar Energy Conversion.

Colloidal InP/ZnSeS-based quantum dots (QDs) are considered promising building blocks for light-emitting devices due to their environmental friendliness, high quantum yield (QY), and narrow emission. However, the intrinsic type-I band structure severely hinders potential photoelectrochemical (PEC) applications requiring efficient photoexcited carrier separation and transfer. In this study, the optoelectronic properties of InP/ZnSeS QDs are tailored by introducing Al dopants in the ZnSeS layer, which concurrently passivate the surface defects and act as shallow donor states for suppressed non-radiative recombination and improved charge extraction efficiency.